基于代谢网络模型研究代谢物交换对共生微生物比例的影响

菌群无处不在，保持合适的菌株比例，是菌群保持结构稳定、发挥功能的必要前提。菌株比例受控于微生物间代谢物交换。考虑到自然环境和菌群的复杂性，本项目拟在合成培养基中研究衣藻-酵母体系的代谢物交换对菌株比例的影响，以期得到广泛适用的结论。.目前实验方法难以直接测定菌间代谢物交换，仅通过实验较难研究菌株比例调控机制。通过计算与实验结合，可以明确共生双菌培养环境中限制菌株生长的代谢物；添加生长限制性代谢物对菌株比例的影响，从而让菌株比例调控的研究更可行。计算与实验结合研究菌株代谢物交换、理解菌株比例调控机理对发展微生物生态学理论、促进微生物工业应用具有重大意义。.本项目已基于博弈论原理和多约束代谢网络模型开发新算法，计划执行计算-实验迭代循环，预测微生物间代谢交换，确定生长限制性交换代谢物，研究菌株比例调控的灵敏性和范围，结合动态模拟结果，从代谢层面分析不同生长限制性交换代谢物调控菌株比例的机理

Microbial communities are ubiquitous, maintaining a proper microbial composition is a pre-requite to the structural stability and well functioning of a microbial community. Microbial composition is controlled by metabolite crossfeeding between microbes. Considering the complexity of natural environment and microbial community, this project aims at studying the impact of crossfeeding metabolites on the composition in an algae-yeast system, expecting to draw some wildly applicable conclusions. ..Due to current difficulty in measuring metabolites crossfeeding between microbes, pure experimental approach may be not capable enough to study the mechanism in manipulation of microbial composition. With a combinatory approach of computation and experiments, we can confirm growth limiting metabolites in co-culture media, and impact of supplementation of growth limiting metabolites on community composition, therefore increase the feasibility of studying manipulation of community composition. The combinatory approach has great significance to microbial ecology theory and promotion of industrial application of microbes..We have completed the development of new algorithms, which were built on game theory and multi-constraint community metabolic models. Following an iterative modelling-testing cycle we will predict microbial metabolic crossfeedings and find growth-limiting metabolites. Then study the range and sensitively of the composition controlled by supplementing each found growth-limiting metabolite. With the results of dynamic simulation, we will be able to study the metabolic level mechanism behind the population manipulation by different growth limiting crossfeeding metabolite.